Mast cells, which are located in the connective tissue of higher vertebrates, store histamine, prostaglandins (local chemical mediators), and proteases within cytoplasmic granules. When stimulated (e.g., by immunological reaction), the contents of these granules are released from the mast cell. Histamine acts only on cells in its immediate vicinity and, upon release, causes blood vessels to dialate, thereby increasing their permiability to serum proteins (e.g., antibodies) and other immune system components (e.g., leukocytes). Histamine is largely responsible for the clinical symptoms of “allergic reactions” such as hay fever (Metzger et al., 1986, Ann. Rev. Immunol. 4:419).
Immunological stimulation is mediated by IgE molecules, IgE being one of the five classes of antibodies found in higher vertebrates. IgE molecules bind with high affinity to an abundant, specific mast cell surface receptor. Bound IgE molecules, in turn, bind specific allergen molecules and considerable evidence indicates that the trigger for the release of the mast cell cytoplasmic granule contents is the allergen mediated cross-linking of two or more bound IgE molecule (Metzger et al., 1986, Ann. Rev. Immunol. 4:419; Ishizaka et al., 1977, J. Immunol. 119: 1589; Isersky et al., 1978, J. Immunol. 121:549; Froese, 1984, Prog. Allergy 34:142; Lewis and Austen, 1981, Nature 293:103).
The mast cell surface receptor consists of three subunits, a heavily glycosylated α-subunit of 50–60 kd exposed to the outer surface of the cell and bearing the IgE-binding site, and two non-glycosylated intramembrane components, the β and γ subunits, of approximately 30 and 20 kd, respectively (Metzer et al, 1986, Ann. Rev. Immunol. 4:419; Froese, 1984, Prog. Allergy 34:142).